Advanced Healthcare Materials最新文献

This study fabricates a functionalized scaffold by cryogenic three-dimensional (3D) printing using an aminated poly-L-lactic acid (EPLA) solution containing nanosilver/zinc-coated black phosphorus (BP@(Zn+Ag)) nanocomposites. The nanocomposites are prepared by a green method of in situ photodeposition of silver and zinc nanoparticles (AgNPs and ZnNPs) on BP nanosheets (BPNs) under visible light irradiation without any chemical reductant. Scanning electron microscope (SEM) and X-ray energy dispersive spectrometer (EDS) confirm the uniform distribution of BP@(Zn+Ag) nanoparticles in the EPLA nanofibrous matrix. The in vitro tests show that the fabricated BP@(Zn+Ag)/EPLA nanofibrous scaffold exhibits excellent antibacterial activity (over 96%) against E. coli and S. aureus, as well as enhanced cell viability and osteogenic activity to facilitate the growth and differentiation of osteoblasts. The in vivo rat calvarial defect model also demonstrates that the BP@(Zn+Ag)/EPLA nanofibrous scaffold promotes new bone tissue formation around the implant site. Therefore, the prepared multifunctional 3D printed BP@(Zn+Ag)/EPLA nanofibrous scaffold has great potential for bone tissue engineering (BTE) applications.

Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, a novel UCA, termed NPs-DPPA(C₃F₈), is innovatively prepared using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent antiangiogenic and antitumor activities, and when combined with C₃F₈, it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C₃F₈) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C₃F₈) exhibits inherent antiangiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C₃F₈) enables simultaneous real-time imaging, tumor assessment, and antitumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C₃F₈) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C₃F₈) offers a novel approach for integrating clinical diagnosis and treatment of TNBC.

Emerging infectious diseases like coronavirus pneumonia (COVID-19) present significant challenges to global health, extensively affecting both human society and the economy. Extracellular vesicles (EVs) have demonstrated remarkable potential as crucial biomedical tools for COVID-19 diagnosis and treatment. However, due to limitations in the performance and titer of natural vesicles, their clinical use remains limited. Nonetheless, EV-inspired strategies are gaining increasing attention. Notably, biomimetic vesicles, inspired by EVs, possess specific receptors that can act as "Trojan horses," preventing the virus from infecting host cells. Genetic engineering can enhance these vesicles by enabling them to carry more receptors, significantly increasing their specificity for absorbing the novel coronavirus. Additionally, biomimetic vesicles inherit numerous cytokine receptors from parent cells, allowing them to effectively mitigate the "cytokine storm" by adsorbing pro-inflammatory cytokines. Overall, this EV-inspired strategy offers new avenues for the treatment of emerging infectious diseases. Herein, this review systematically summarizes the current applications of EV-inspired strategies in the diagnosis and treatment of COVID-19. The current status and challenges associated with the clinical implementation of EV-inspired strategies are also discussed. The goal of this review is to provide new insights into the design of EV-inspired strategies and expand their application in combating emerging infectious diseases.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H₂O₂) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO₂@Au hydrogel system (CuO₂@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO₂@Au Gel is constructed by embedding therapeutic CuO₂@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO₂@Au in CuO₂@Au Gel is capable of self-supplying H₂O₂ and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO₂@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation.

The development of nanoassemblies, activated by the tumor microenvironment, capable of generating photothermal therapy (PTT) and amplifying the "ROS (·OH) storm," is essential for precise and effective synergistic tumor treatment. Herein, an innovative cascade-amplified nanotheranostics based on biodegradable Pd-BSA-GOx nanocomposite for NIR-II photoacoustic imaging (PAI) guides self-enhanced NIR-II PTT/chemodynamic therapy (CDT)/starvation synergistic therapy. The Pd-BSA-GOx demonstrates the ability to selectively convert overexpressed H₂O₂ into strongly toxic ·OH by a Pd/Pd²⁺-mediated Fenton-like reaction at a lower pH level. Simultaneously, the GOx generates H₂O₂ and gluconic acid, effectively disrupting nutrient supply and instigating tumor starvation therapy. More importantly, the heightened levels of H₂O₂ and increased acidity greatly enhance the Fenton-like reactivity, generating a significant "·OH storm," thereby achieving Pd²⁺-mediated cascade-amplifying CDT. The specific PTT facilitated by undegraded Pd accelerates the Fenton-like reaction, establishing a positive feedback process for self-enhancing synergetic PTT/CDT/starvation therapy via the NIR-II guided-PAI. Therefore, the multifunctional nanotheranostics presents a simple and versatile strategy for the precision diagnosis and treatment of tumors.

Cardiovascular diseases are currently the most common cause of death in developed countries. Due to lifestyle and environmental factors, this problem is only expected to increase in the future. Reactive oxygen species (ROS) are a key player in the onset of cardiovascular diseases but also have important functions in healthy cardiac tissue. Here, the interplay between ROS generation and cardiac mechanical forces is shown, and the state of the art and a perspective on future directions are discussed. To this end, an overview of what is currently known regarding ROS and mechanosignaling at a subcellular level is first given. There the role of ROS in mechanosignaling as well as the interplay between both factors in specific organelles is emphasized. The consequences at a larger scale across the population of heart cells are then discussed. Subsequently, the roles of ROS in embryogenesis, pathogenesis, and aging are further discussed, exemplifying some aspects of mechanoregulation. Finally, different models that are currently in use are discussed to study the topics above.

In oncological nanomedicine, overcoming the dual-phase high interstitial pressure in the tumor microenvironment is pivotal for enhancing the penetration and efficacy of nanotherapeutics. The elevated tumor interstitial solid pressure (TISP) is largely attributed to the overaccumulation of collagen in the extracellular matrix, while the increased tumor interstitial fluid pressure (TIFP) stems from the accumulation of fluid due to the aberrant vascular architecture. In this context, metal-organic frameworks (MOFs) with catalytic efficiency have shown potential in degrading tumor interstitial components, thereby reducing interstitial pressure. However, the potential biotoxicity of the organic components of MOFs limits their clinical translation. To circumvent this, a MOF-like photocatalytic nanozyme, RPC@M, using naturally derived cobalt phytate (CoPA) and resveratrol (Res) is developed. This nanozyme not only facilitates the decomposition of water in the tumor interstitium under photoactivation to reduce TIFP, but also generates an abundance of reactive oxygen species through its peroxidase-like activity to exert cytotoxic effects on tumor cells. Moreover, Res contributes to the reduction of collagen deposition, thereby lowering TISP. The concurrent diminution of both TISP and TIFP by RPC@M leads to enhanced tumor penetration and potent antitumor activity, presenting an innovative approach in constructing tumor therapeutic nanozymes from natural products.

Bioluminescence imaging (BLI) is a powerful technique for noninvasive monitoring of biological processes and cell transplantation. Nonetheless, the application of D-luciferin, which is widely employed as a bioluminescent probe, is restricted in long-term in vivo tracking due to its short half-life. This study presents a novel approach using amino acid-encoded building blocks to accumulate and preserve luciferin within tumor cells, through a supramolecular self-assembly strategy. The building block platform called Cys(SEt)-X-CBT (CXCBT, with X representing any amino acid) utilizes a covalent-noncovalent hybrid self-assembly mechanism to generate diverse luciferin-containing nanostructures in tumor cells after glutathione reduction. These nanostructures exhibit efficient tumor-targeted delivery as well as sequence-dependent well-designed morphologies and prolonged bioluminescence performance. Among the selected amino acids (X = Glu, Lys, Leu, Phe), Cys(SEt)-Lys-CBT (CKCBT) exhibits the superior long-lasting bioluminescence signal (up to 72 h) and good biocompatibility. This study demonstrates the potential of amino-acid-encoded supramolecular self-assembly as a convenient and effective method for developing BLI probes for long-term biological tracking and disease imaging.

Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment.